Computer algorithms and methods for product safety

ABSTRACT

The invention comprises systems, methods and a computerized, data management device for creating and using data relating to a medical or non-medical product or device to enhance the safety of the product or device. A vast amount of data regarding adverse events associated with a particular product or device is analyzed to identify new essential adverse events associated with the product or device. At least one database anew essential adverse event information is created and utilized, and new characteristics of or uses for the product or device related to the new essential adverse event information are determined. Adverse event information is gathered for a large number of population sub-groups. The system may also be programmed to incorporate the information into intellectual property and contract documents. Manufacturers and/or distributors can include the proprietary information in consumer safety information, which accompanies the product or device, or which is provided to patients, users, consumers and the like, or in the case of certain medical products or devices, to prescribers of those products or devices. The system and methods also provide for commercializing the essential adverse event information.

REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. application Ser.No. 10/081,705, filed Feb. 21, 2002, the entire contents of which ishereby incorporated by reference, and claims the benefit of U.S.Provisional Application No. 60/270,697, filed Feb. 22, 2001, whichfiling date is claimed herein, and the content of which is hereinincorporated by reference.

FIELD OF THE INVENTION

The present invention involves the fields of products, including drugs,medicaments, biologicals, devices, food additives, chemicals and otherproducts or devices, that may have essential adverse events, as well ascomputer databases for generating, storing, analyzing and processinginformation related thereto.

BACKGROUND OF THE INVENTION

Computers, systems and methods for screening databases to determine newadverse events and to develop proprietary new uses and proprietary kitscontaining warnings pertaining to the new adverse event information havebeen described in U.S. Pat. No. 6,219,674 and U.S. patent applicationSer. No. 09/804,289. However, the systems and methods described in the'674 patent were less than ideal because not all adverse eventinformation is commercially valuable.

In order for adverse event information to be valuable it must bepatentable (i.e. proprietary) by being novel, non obvious and havingutility. Likewise, the systems and methods described in the '289 patentwere less than ideal because, even if the adverse event data ispatentable, it is not commercially valuable unless it is essential, thatis, the information must be such that all manufacturers would need toinclude it with the sale of the corresponding product. Otherwise,manufacturers would continue to sell their products without the subjectinformation. Conversely, if one were to simply patent all new uses forthe product, drug, and the like, considerable time and money would beconsumed, but there would by a low probability for commercial orfinancial return on the whole.

The government has carefully established codes and rules under which,for example in the medical field, manufacturers and/or distributors arerequired to notify or warn the public of known adverse events whichcould occur when certain products, including drugs, medicaments and thelike, are ingested or used by human or veterinary patients. Regulationsalso apply to chemical products, including food supplements, which maybe absorbed, ingested or inhaled. Similar notice or warnings must beattached to devices, particularly to medical devices, Moreover, if thewarnings are not present, the product or device not only must beimmediately removed from use by, and availability to, the public, butalso significant fines and penalties can be levied against themanufacturer and/or distributor of the product or device for its failureto provide adequate notice and warning to the public. In addition,because such manufacture and/or distribution was permitted without therequired notice or warning, the manufacture and/or distribution waspracticed in violation of the law. As a result, those manufacturersand/or distributors risk criminal and/or civil liability to anyoneadversely affected by the product or device during the time when it wason the market.

The government has failed to establish mechanisms by which products anddevices are adequately screened for safety, i.e., for the possibility ofessential adverse events which could affect the safety of the patientusing the product or device. This is particularly true for medicalproducts and devices. The screening that is conducted by manufacturersand/or distributors of such products and devices is typically small inwale and incomplete for all possible adverse events. Consequently, untilthe present invention, there has been a need in the art for reliablescreening methods to eliminate or minimize the possibility of anessential adverse event that could affect a patient or consumer using aproduct or device, so that the consumer can trust that the product ordevice is “safe.”

In addition, the prior art has failed to contemplate business methodswhich involve detecting essential adverse events relating to a productor device, and then offering the refined proprietary data from suchscreens to the manufacturers and/or distributors of the product ordevice. Once the existence of such essential adverse data is known tothe manufacturer and/or distributor, they are obligated to inform thepublic of the potential adverse event, or they must remove the productor device from the market. Because manufacturers are currently producingand distributing products and devices without restrictions on their use,they are available for use in screens to develop essential adverse eventdata which when refined, would become proprietary. Thus, there alsoexists a substantial market for such refined, proprietary, essentialadverse event data, and for the methods, systems and devices by which itis obtained, which would (1) meet the need in the art for steps whichwould enhance public safety with regard to the use of products anddevices, and (2) offer to manufacturers and/or distributors of productand/or devices as way to (a) significantly improve public safety, (b)permit their products and devices to remain on the market, and (c)reduce their risk of liability for the occurrence of an adverse eventwith the use of their products or devices.

SUMMARY OF THE INVENTION

The current invent permits not only ways of screening for new,previously unrecognized adverse events associated with the use of aproduct or device, but also a method, system and device for determiningwhich new adverse events and new uses are “essential.” The method,system and device permit a technician or computerized system to detectnew essential adverse events and identify new useful characteristics oruses for a product or dev and commercialize the essential adverse datainformation.

In some instances a manufacture or distributor is given the option ofadding notifications or warnings that a product or device is associatedwith an essential adverse event, or they can perform safety studies toshow the product is safe in light of the newly recognized, essentialadverse event (essential methods of screening a product fin safety).Thus, the invention relates to data processing methods and system fordeveloping product safety information to be included in the packageinformation which would accompany a commercial product or device. Thecurrent methods and system further provide for the detection anddevelopment of methods of screening a product or device for consumersafety.

In preferred embodiments, the data processing system comprises; at leastone adverse event database for storing adverse event data associatedwith a product or device; it processor for accessing and analyzing thedata to assist in identifying new essential adverse events associatedwith the product or device and to assist in identifying at least one newuseful characteristic of, or use for, the product or device responsiveto identification of at least one new essential adverse event associatedwith the product or device; an adverse event information storage devicefor storing the new essential adverse event data identified by theprocessor; a computer for requesting and receiving adverse eventinformation from the processor; and a user interface for interfacingwith the processor and the computer.

The present invention is further embodied by a method for creating andusing data associated with a product or device comprising: accessing atleast one adverse event data source that stores adverse event dataassociated with a product or device; analyzing the adverse event data toidentify new essential adverse events associated with the product ordevice; analyzing data from the data source to identify at least one newuseful characteristic or use for the product or device responsive toidentification of at least one new essential adverse event; creating atleast one essential adverse event information database, wherein theadverse event information includes at least one new characteristic oruse; and commercializing essential adverse event data stored in theessential adverse event information database.

The invention is also embodied by a method of establishing at least onenew use for a product or device comprising: comparing adverse event dataassociated with a product or device with previously known adverse eventdata associated with the product or device; observing at least one newadverse event associated with the product or device; determining whetherthe new adverse event associated with the product or device is anessential adverse event; and identifying at least one new usefulcharacteristic oh or use far, the product or device responsive to thedetermination that the at least one new adverse event associated withthe product or device is an new essential adverse event.

In addition, the invention is embodied by a computer far managingproduct or device related data comprising: at least one adverse eventdatabase storing adverse event data associated with a product or device;a processor for accessing and analyzing the data to assist inidentifying new essential adverse events associated with the product ordevice and to assist in identifying at least one new usefulcharacteristic of or use far, the product or device responsive toidentification of at least one new essential adverse event associatedwith the product or device; and an essential adverse event informationstorage device for storing essential adverse event data including the atleast one new essential adverse event associated with the product ordevice, and the at least one new characteristic of, or use for, theproduct or device identified by the processor.

Moreover, the method and system farther provide for commercializing theessential adverse, event information.

Further, the invention is embodied by methods and systems by which thedetected information is formatted and compiled into contract documents,which are then used in licensing the essential adverse event informationto manufacturers and/or distributors, who can then include the essentialadverse event information in their product information, which isprovided to consumers or prescribers of the product or device. Moreover,such contract documents can be used to license the essential adverseevent information to potential competitors of the manufacturer and/ordistributor.

The embodied invention also provides marketing and packaging methods, inwhich the use of the subject product or device is restricted by alicensing agreement or contract, which would exclude using the productor device for the detection and patenting of essential new adverse eventinformation.

The invention also pertains to any product or device created using theessential adverse event data of the method, system or device of thepresent invention; well as uses therefore.

The invention also provides a kit containing the product device, andlabeling notifying the user of at least one new essential adverse eventfor the product or device. Additionally provided are methods comprisingusing the kit in accordance with a new characteristic of, or use for,the product or device.

The invention is especially useful in detecting and preventing essentialadverse events related to, or caused by, medical products includingdrugs, medicaments and biologicals and medical devices.

Other objects, features and advantages of the present invention will beclear to those skilled in one or more of the relevant arts, based on theteachings and guidance presented herein.

DESCRIPTION OF THE DRAWINGS

The foregoing summary, as well as the following detailed description ofthe invention, will be better understood when read in conjunction withthe appended drawings. For the purpose of illustrating the invention,there are shown in the drawings, certain embodiments which are presentlypreferred. It should be understood, however, that the invention is notlimited to the precise arrangements and instrumentalities shown.

FIG. 1 is a schematic view of a first embodiment of a system accordingto the present invention.

FIG. 2 is a schematic view of a further embodiment of a system accordingto the present invention.

FIG. 3 is a schematic view of a further embodiment of to systemaccording to the present invention.

FIG. 4 is a flow chart illustrating the method according to the presentinvention.

FIG. 5 is a first preferred specific application of the methodrepresented in FIG. 4.

FIG. 6 is a further preferred specific application of the methodrepresented in FIG. 4.

DETAILED DESCRIPTION OF THE INVENTION

The inventor's prior invention, U.S. patent Ser. No. 09/449,178 (nowallowed) describes a computer system and method for deriving new usesbased on new adverse events, which also finds application in the presentinvention. However, the currently embodied system and method of theinvention provides for the further purification or refinement of adverseevent information to develop new proprietary uses for a product, such asa drug, or for a device. The system and methods provide detecting“essential” adverse event information or “essential” new uses based onthe adverse events or “essential” new methods of screening a product forsafety.

Referring to the drawings wherein like references indicate like elementsthroughout the several views, there is shown in FIG. 1 a first, system10 constructed in accordance with the present invention. System 10includes at least one adverse event database 12, at least one essentialadverse event database 12′ and a server 14. Depending upon the source,the adverse event database(s) 12 may be accessed by server 14 free ofcharge or for a fee. Essential adverse event database 12′, preferablycontains large amounts of data regarding a particular “essential”medical or non-medical product or device.

The term “medical” as used herein shall be construed to mean drugs,vaccines, non-vaccine biologicals, medical devices and any othermedically-related goods and therapies. Drugs and biologicals as theterms are herein used within, the term “medical product,” are intendedto encompass any known, or as yet unknown, class of drug, medication orbiological therapeutic (including inhibitors, preventors, enhancersactivators, stimulants, catalysts, promoters, regulators, and the like).These can be categorized by their effects on an organ system, such ascardiac, respiratory, renal etc. Drugs and biologicals are alsoclassified by their chemical composition, e.g., sulfa drugs, penicillinderivatives, vaccines, immune stimulants, antibiotics, etc. In addition,they can be classified according to their activity, e.g., diuretic,antibiotic, beta-blocker, etc.

Medical devices can be similarly classified by those of ordinary skillin the art, e.g., medical devices may be grouped as defibrillators, EKGmachines, infusion pumps, CT machines, etc. To further assist in thecategorization process, those skilled in the art may consult medicalscience resources such as medical libraries or online authorities suchas MEDLINE® and the like to locate articles, books or other printed orelectronic publications the subject of interest such as the non-limitingexample of Goodman and Gilman's “The Pharmacological Basis ofTherapeutics.”

“Non-medical product or device” shall be construed to mean anynon-medically-related product or device that may cause harm to aconsumer including, without limitation, foods, food additives,beverages, vitamins, alcohol, tobacco, cosmetics, mechanical devices andchildren's toys, personal and household cleaning products, and otherchemicals such as paints and related coatings, insecticides, herbicidesand industrial chemicals.

Because of the large volume of data that they contain, preferred adverseevent databases may include those of insurance companies, managed careorganizations, pharmaceutical and medical device manufacturers and/ordistributors, public health departments, hospitals and the like.Typically, each adverse event recorded in such databases links theadverse event with demographic information such as hut not limited to,the age, sex and race and, frequently, one or more physical conditionfactors of the individual that experienced the essential adverse event.The result is that adverse event database 12 may contain thousands oreven millions of items of data. Such vast repositories of informationenable the data to be analyzed to generate statistically revelant andreliable information relating to age, gender, racial physical conditionor other subgroup. The essential adverse event database 12′ is arefinement of the adverse event data procured from the adverse eventdatabase 12, based upon selection of adverse data that is “essential” asdefined below.

Server 14 preferably includes a shadow storage device 16, a processor18, a user interface 20 and an essential adverse event informationstorage device 22. Shadow storage device 16 gathers and stores essentialadverse event data received from the adverse event database(s) 12.Processor 18 comprises any computer processing means suitable forexecuting the operations of the present method as described hereinafter.Use interface 20 includes any suitable input/output (I/O) equipment.Essential adverse event information storage device 22 stores adverseevent information that is generated by processor 18 responsive toanalysis of the essential adverse event data stored in shadow storagedevice 16. The shadow and essential adverse event information storagedevices 16, 22 may be any memory devices capable of storing largeamounts of information. Lastly, system 10 includes a user computer 24for interfacing with user interface 20. User computer 24 is preferablyany commercially available personal computer workstation or the likewhich can exchange information with user interface 20 in the manner wellknown in the art.

If the event data relating to a product or device is both essential anddesired, the essential adverse event data in adverse event database 12′can be collected using the ICD and other disease codes on admission,discharge, pharmaceutical sales, physician visit records or other knownsources. The system of the present invention also accommodates andprocesses animal safety test data such as animal toxicity data.

Through operation of system 10 and the other systems described herein,the data extracted from adverse event database 12 is analyzed bysuitable programming of processor 18 to produce useful essential adverseevent information that collected into essential adverse event database12′ and is storable in essential adverse event information storagedevice 22. For example, the adverse event database stores information onfrequency of essential adverse events, such as but not limited to,death, illness, hospitalization, office visits, disability, missed work,medical costs, abnormal lab results and surgeries in individualsreceiving the product or device in question, and this information can becompared to the observed adverse event rate in the same persons beforereceiving the mea cal product or in persons of similar characteristics(i.e., a control group). The analysis is performed on different exposurerates including, but not limited to the amount, duration and timing ofexposure to the product or device.

The “adverse events” refer to, for example, damage or alteration to anyorgan system, including the non limiting examples of cardiac,respiratory, gastrointestinal, endocrine, muscular, skeletal, liver,renal, spleen, neurological, skin, blood, immune, and bone narrow. Theseadverse events further include the development of new diseases,including the non limiting examples of seizures, cancers, heart disease,arrhythmia, autoimmune disease, and allergy. Moreover, failure of aperson to respond beneficially to a drug can be considered an adverseevent. Preferably, the adverse event (or new use) is one other than onerelated to dosing including the timing of dosing (or optimizing dosing).

The database to be screened for new adverse events comprises adverseevent information relating to the use of products in or devices onhumans or animals. While human data is more valuable for determining newuse in humans, it is possible that new adverse events detected inanimals can be used to develop new product characteristics or uses inhumans. An example is detection of birth defects, or drag interactionsin animals, which preferably leads to new uses comprising restricted usein pregnant humans or humans taking certain drugs.

Databases of adverse event information can be created by screeninganimal models of specific human diseases and cell culture models ofhuman diseases for the potential new adverse events, in this situationan animal model of human disease is exposed to the product and thefrequency or severity of the disease is recorded compared to a controlgroup. Ideally the product is exposed to as many different animal modelsof human diseases as possible or feasible.

In a similar manner a culture of cells can be exposed to a product inmany instances. This is easily accomplished, if the product is a drug,chemical, or emits radiation. The cells may be normal cells,premalignant or malignant cells. One can compare the outcome of producton the cells to that of the effect on control cells. Endpoints includethe non limiting examples of cell death, cell mutation and celldivision. Ideally the product or device is exposed to as many differentanimal models of human diseases as possible or economically feasible.

One can use the data from the database to compare to previously knownadverse events to determine new adverse event information. The order bywhich one checks for an adverse event can vary, and any order that issuitable is acceptable. For example, one can hypothesize that a productcauses one or more adverse events. One can then analyze the data to seeif the product causes an adverse event, and then determine if theadverse event is new. Alternatively, one can hypothesize that a productcauses an adverse event and then check databases to see if it has beenreported that the product is associated with an adverse event. If theassociation has not been reported than one can screen raw adverse eventdata/databases to see if the product is associated with the adverseevent. If data does not exist to test the hypothesis using available rawadverse event data, then new data can be generated in the form of astudy. In most cases, this would involve animal toxicity studies sinceperforming prospective studies in humans to prove adverse events isgenerally unethical.

By “raw data,” as used herein, means data before it is processed andanalyzed. For example, the raw efficacy or adverse event data relatingto a drug would include all of the collected data, which is linked toindividuals who used the drug, or in some instances for a product suchas tobacco, for those exposed to the product. This raw data comprises,e.g., the individual's weight, height, race, lab results, medicalconditions and length of use or exposure to a product or device. Bycontrast, “processed data” means analyzed data that has been categorizedor qualified to meet the requirements or standards of a particularsituation

In a preferred embodiment, one searches existing adverse event databasesfor adverse events, then determines if associations discovered are new.An additional study can be performed to verify the finding. In anotherpreferred embodiment, one can hypothesize about certain adverse events,and then determine if they have been reported. If they have not, thenraw adverse event data would be analyzed to determine if there is anassociation.

Additional adverse event information may also be derived from subgroupanalysis. Subgroup analysis is performed to determine specific high riskgroups who may be at increased risk of having an essential adverseevent. Subgroups include persons with similar characteristics, such asbut not limited to, sex, age, race, weight, height, percent body fat,genetic characteristics, pregnancy status, allergies, additional medicalproblems, use of additional medical products (including devices), pastmedical history, family history, social history, occupation, use ofalcohol, tobacco, recreational drugs, and history of abnormal lab testssuch as EKG, chest x-ray, liver function test and kidney function test.Similarly, subgroups are intended to include without limitation highrisk associated groups such as high or low temperatures, chemicals,surfaces, pressures, electricity and sparks; or contact of the productor device with one of the group consisting of skin, eyes, ears,respiratory surfaces, gastrointestinal surfaces and mucous membranes ofthe consumer, or to a subpopulation group selected from the groupconsisting of children, pregnant women, consumers with specificallergies or medical conditions and animals. Preferably this demographicdata, i.e., sub group information, is available through history andphysical, when no additional laboratory test is needed for a new use.The subgroup analysis can include groups that were not represented orwere under-represented in safety studies that were required formarketing approval or were done around the time of market introduction.For example, a drug may be approved for use in persons over the age of18. However, people under 18 may also receive the drug. In such case,packaging for the drug may not include sufficient warnings for personsunder 18, in general, and subgroups of persons under 18, in particular,that are at greater risk of essential adverse events linked to usage ofthe product or device.

Studies, as described above and in other sections of this document,however do not prove a product or device causes an adverse event, onlythat the adverse event and the product or device are associated, in someinstances there may be a direct link. For example, wealth or standard ofliving is associated with certain adverse events. Money does not causethe adverse events, but it allows wealthy individuals to buy productsthat cause a specific adverse event. If an epidemiology study does showan association between an adverse event and a product or device, thenthere is a risk that the associated product or device caused the adverseevent.

This risk exists even if the association is not statisticallysignificant. However the risk is greater if a statistically significantassociation exists. Since some of the associations are true causalrelations, knowledge that a risk exists has utility since one can avoidthe risk when one knows it exists.

Ideally, systems according to the invention track large numbers ofvariables to locate groups at high risk of essential adverse events. Asa non-limiting example, the systems are configured to track peopletaking multiple different drugs to determine whether a toxic adverseevent occurs in people taking all of the drugs at once. The systemsutilize statistical formulae to identify groups at high or low risk ofessential adverse events. Preferably the database of adverse eventsassociated with a product contains multiple different adverse events andis not limited to a single type, such as diabetes, birth defects, or thelike.

The systems according to the invention also optionally collect andanalyze efficacy data. The benefit of the product or device in certainsubgroups can thus be measured by observing the frequency of theintended benefit (e.g., decreased death, stroke, kidney failure, and soon). Benefits also include reductions in costs where the costs mayinclude, without limitation, costs of the product or device, expensesand lost productivity. By using the data from the risks and benefits,one can determine the risk/benefit for persons in any particularsubgroup.

This information can be highly stratified to enable, in addition topreviously known uses, new, different or more precise uses for a productor device. For example, a dose of a drug or biologic, the frequency ormanner of use of a device, or the setting of a device such as apacemaker may be precisely prescribed to accommodate the individualneeds of particular subgroups.

Targeted searches can be performed and their data analyzed by thesystems of the present invention. For example, if it is discovered fromone adverse event database 12 that persons receiving a medical productare at increased risk of dying of liver failure at a certain dose ofmedication or when taking the drug in combination with other drugs, thenone can verify the findings using a second adverse event database 12.Adverse event data from either adverse event database can also beconfirmed in animals or by prospective clinical trials in humans.Targeted searches can also be done after case reports of adversereactions, discovery of adverse events in animals, adverse eventsdiscovered in similar products and possible adverse found in smallstudies.

Consistent with the invention, any number or variety of proprietarydatabases are storable on essential adverse event information storagedevice 22. For instance, a first proprietary database created containinginformation about a particular product's or device's adverse events and,optionally, risk benefits and cost benefits of the product or device.The data from that database is crossed, linked or compared with adatabase of knowledge already accumulated on the product or device thatmay also be stored on essential adverse event information storage device22. Sources of prior known essential adverse events can include packageinserts, the Physician's Desk Reference, The Merck Manual, data fromregulatory agencies such as the FDA, and published literature found ondatabases such as MEDLINE®. In the future it is contemplated thatdatabases of patents and patent applications will also contain knownadverse events. Likewise, the databases can comprise commercial or salesdata. New findings on essential adverse reactions can thus be determinedthrough appropriate comparison and/or interpretation of the databases.

The newly derived knowledge can include, without limitation, catalogs ofnew adverse events, specific frequency of adverse events, druginteractions and side effects subgroups such as those mentioned above.For instance, a new essential adverse event can mean newly discoveredadverse reaction such as the discovery of an increased rate of seizuresassociated with a drug, improved information such as more accuratecalculation of the rates of seizures in a group or subgroup, or thediscovery of an increased rate of seizures in patients taking the drugalong with one or more additional drugs.

FIG. 2 represents a further preferred embodiment of as system accordingto the invention identified by reference numeral 110. System 110 isconstructed and functions substantially similarly to system 10 of FIG. 1with the exception being that the shadow storage device 16 and essentialadverse event information storage device 22 of system 10 are integratedinto a single shadow storage device and essential adverse eventinformation storage device 16, 22 on server 114.

FIG. 3 represents a further preferred embodiment of a system accordingto the invention identified by reference numeral 210. System 110 also asconstructed and functions substantially similarly to system 10 ofFIG. 1. However, unlike systems 10 and 110, system 210 draws itsessential adverse event data from an internal rather than an externalsource; that is, server 214 of system 210 directly supports essentialadverse event database(s) 12′. System 210 graphically depicts asituation wherein a holder of a substantial body of adverse event dataitself analyzes such data using processor 18 and creates one or moreadverse event information databases that are stored on essential adverseevent information storage device 22.

Exemplary users of system 210 may include, for example, insurancecompanies, managed care organizations, pharmaceutical and medical devicemanufacturers and/or distributors, public health departments, hospitalsand the like. Although illustrated as separated devices, it is alsocontemplated that essential adverse event database(s) 12′ and essentialadverse event information storage device 22 may be integrated into asingle storage device.

FIG. 4 is as flow-chart that embodies the essential method steps of thepresent invention that are executed by each of systems 10, 110 and 210.At step 26, the adverse event database(s) 12 are accessed by server 10,110 or 210 (at a fee or free of charge) to obtain desired adverse eventdata therefrom. In systems 10 and 110, the adverse event database(s) 12are external to the servers 14 and 114. Hence, servers 14 and 114desirably store the data received from databases 12 in shadow storagedevices 16. Server 214, by contrast, accesses it internal adverse eventdatabase(s) 12 for the desired data.

The desired adverse event data having been accessed, the processor 18 ofsystems 10, 110 and 210 then analyzes the data, as described above, toidentify previously known and new essential adverse events, as indicatedat step 28. At step 30, the processor 18 farther processes the analyzedadverse event data to create useful proprietary essential adverse eventinformation, such as any of the kinds mentioned above. Moreparticularly, in creating the proprietary adverse event informationdatabase at step 30, or more preferably an essential adverse eventinformation database, at step 30′ (not shown), processor 18 preferablypossesses logic whereby it categorizes the newly-discovered essentialadverse event(s) associated with a particular product or device that areidentified at step 28 and also identifies at least one new use for theproduct or device responsive to the identification of at least one newessential adverse event(s) associated with the product or device. Theprocessor 18 then stores the essential adverse event information as oneor more databases in essential adverse event information storage device22.

According to presently preferred embodiments of the invention, the dataretrieved from adverse event database(s) 12 is processed and analyzed bya centralized processor 18 on server 14, 114 or 214 and the analyzeddata is stored at an essential adverse event information storage devicealso supported by server 14, 114 or 214. Alternatively, the proprietorsof servers 14, 114 or 214 license proprietary software to users of usercomputers 24 that perform the functions of processor 18. Such softwareis loaded onto the user computers 24 to execute the adverse event dataanalyzing and other processing functions of processor 18 described aboveand the generated useful adverse event information may be stored at theuser computers 24. In any case, servers 14, 114 and 214 can be directlyconnected by a user interface 24 such as but not limited to a modem.

It will be understood that the servers 14, 114 and 214 may also beindirectly connected to user computers 24 via one or more other servers,a central computer or other system designed to link computers or otherprocessing machines. Ideally, the information is transferred digitallybetween servers 14, 114 and 214 and user computers 24. Alternatively,however, it is transmitted in analog form by a modem along standardtelephone lines, it is further understood that the information can alsobe transferred by disk, printed and then scanned in or, alternatively,manually re-keyed.

Preferably, the use computers 24 and their associated printers (notillustrated) are sufficiently sophisticated to organize and pint allinformation generated by the systems 10, 110 and 210 in virtually anydesired format and on essentially any desired printable medium that isprinted by the printers. However, certain product labels and packageinserts that incorporate the information can be manually type facedusing typesetting or other conventional printing techniques. The systemalso formats the data for submission to regulatory agencies such as theFDA.

The proprietary information that is generated by the systems of thepresent invention is superior in many ways to the limited, and generallystatic, adverse event data and databases heretofore known in the art. Inrespect to medical products in particular, the volume of data and thedegree to which the data may be stratified and studied, the systemsaccording to the invention far exceed the capabilities of FDA-requiredpre-marketing studies for medical products. To illustrate, a typical FDApre-marketing study generally involves study populations of less thanabout 5000 and normally less than about 2000 participants. In contrast,the adverse event data that is amassed and analyzed pursuant to theinvention contains information on far larger numbers of people receivingthe medical product. Representative populations studied using thepresent system in virtually all practical medical product scenarioscomprises at least 5000 and is analyzed in any desired increment suchas, for example, 5,000; 10,000; 50,000; 100,000; 200,000; 1 million ormore.

The systems of the present invention will additionally provide a betterappreciation of delayed or latent essential adverse events caused byproducts or devices long after initiation of treatment or aftertreatment has been discontinued. Using the present systems,post-exposure follow-up of a product or device is analyzed in anydesired increments of time. For instance, selected post-exposure studyperiods may be as brief as a few minutes or hours to considerablylengthier periods, such as 1 day, 2 days 7 days, 10 days, 30 days, 90days, 180 days, year, 3 years, 5 years, 10 years or more.

Risk/benefit analyses may also be readily performed using the methodsand systems described herein. Acceptable essential adverse eventthresholds may be established and studied for a product or device. Theessential adverse event thresholds may be selected to be at any desiredincidence level, e.g., 1:10,000,000; 1:1,000,000; 1:100,000; 1;10,000;1:1,000; 1:100, above which use of a product or device may exceed itsbenefit for a general or specific population group. The essentialadverse event thresholds serve as limits for single or aggregated newlydiscovered adverse events. For example, an essential adverse eventthreshold of 1 occurrence in 1000 persons may be established as anacceptable level of occurrences.

If 2 occurrences are observed in the target population then theessential adverse event threshold is exceeded and the product or deviceis deemed unsafe or commercially impractical for use by persons in thatgroup. Likewise, 10 new similar or dissimilar essential adverse eventsrelating to the product or device may be observed, in the target group,but none of the individual new essential adverse events occurs more thanonce in 10,000 persons. In the aggregate, therefore, the 10 occurrencesdetected in a total study population of 10,000 persons corresponds to aratio of 1:1000 which equals, but does not exceed the acceptableessential adverse event threshold for the product or device underscrutiny. In this instance, the product is deemed safe and commerciallyviable for use in the targeted population group.

The present systems and methods also enable ready comparisons betweentarget populations that receive treatment with a product or device, andexperience essential adverse events, with untreated control groups thatexperience similar essential adverse events. For example, a target grouptreated with a certain vaccine that acquires diabetes may be comparedwith an otherwise identical but unvaccinated control group that alsoacquires diabetes. Increased incidences of diabetes in the target groupthus may be attributable to the vaccine.

Systems 10, 110 and 210 may be programmed to establish any desiredacceptable increased rates of essential adverse event occurrences in thetreated target group versus the untreated control group, e.g., 2%, 5%,10%, 20%, 30%, 50%, 75%, 100%, 150%, 200%, 300%, 400%, 600%, 800%,1,000% or more, above which treatment would be contraindicated in thetarget group. Preferably, the system analyzes data using any desiredstudy design. For example, a case control study design may be used wherethe frequency of using a product or device in a group with the targetdisease is compared to the frequency of using a product or device in agroup of controls. The studies may include prospective clinical trialsand retrospective follow-up of clinical trials, as well as cohortanalysis of people not in clinical trials. The studies may, or may not,include efficacy for the intended use as in treatment of a specificdisease. The studies may also be part of a pre-approval orpost-marketing study regulated by the FDA or similar regulatory body.Conversely, the studies may be unaffiliated with FDA-sanctioned clinicaltrials.

Returning to FIG. 4, the adverse event information stored in essentialadverse event information storage device 22 is commercialized.Commercialization of the useful essential adverse event information maytake on an assortment of forms as indicated in FIGS. 5 and 6.

Users of servers 10, 110 and 210 may include individual, a corporation,partnership, government agencies, research institutions or any otherpersons or entities that may have an interest in or need for new anduseful essential adverse event information. Non-limiting examplesinclude manufacturers and/or distributors of products or devices,insurance companies, health maintenance organizations and public healthdepartments. In the case of manufacturers and/or distributors ofproducts or devices, such manufacturers and/or distributors may use theinformation in the manufacture and/or distribution of their ownproducts, or may license the information to their competitors.

As indicated by step 26′ in FIGS. 5 and 6, at the request any of thesepersons or entities or on its own behalf, the owner or licensee ofserver, 14, 114 or 214 accesses and retrieves raw adverse event productdata from adverse event database(s) 12. At step 28′ the server analyzesthe retrieved data to identify new essential adverse events regarding aproduct or device, to conduct cost/benefit analyses related to the newlydiscovered essential adverse events or to perform any other desiredanalysis of the raw data. At step 30′ the server creates one or moreproprietary essential adverse information databases that are stored inessential adverse information storage device 22. At step 32′ in FIG. 5the licensee or owner or owner of server 14, 114 or 214 commercializesthe essential adverse event information in essential adverse informationstorage device 22 by selling or licensing the proprietary information toa third party. The third party communicates with system 10, 110 or 210through user computer 24. The user computer interfaces with userinterface 20 to make requests for information to and to receiveinformation from the processor 18 of server 14, 114 or 214.Interpretation of the received information may be performed by the thirdparty, an independent contractor, the owners or licensees of server 14,114 or 214 or the owner(s) or licensees of the essential adverse eventdatabase(s) 12.

Practical, but non-limiting, examples of possible users of systems 10,110 or 210 and the method depicted in FIG. 5 include manufacturersand/or distributors of products or devices, holding companies, venturecapital companies or other companies or individuals seeking tocapitalize on ownership of a portfolio of new product information thatmay be of commercial value. The users may use the information to seekpatent, or other intellectual property protection for the information.The systems 10, 110 and 210 and the methods depicted in FIGS. 5 and 6are especially useful for creating proprietary information and productsor devices. The systems and methods of the present invention can assistin preparing information for a patent application and can assist indocumentation of the invention, including inventors, date of invention,progress of the development of invention. As used herein, proprietaryinformation shall be construed to mean information that is used orintended to be used for establishing or claiming specific intellectualproperty rights, For example, the proprietary information can be used inthe creation of intellectual property, sale or licensing documents; thatis, the proprietary information may comprise textual or graphicalcontent that may be incorporated into patent applications. A‘proprietary new use’ means a new use, in which one has or is seekingintellectual property rights, i.e., a patent.

It is not the intent of this invention to encompass an “expanded use”relating to an unexpected phenomenon associated with a product ordevice. “Expanded use” is used herein to mean other uses for a productor device in addition to currently known uses for the product or device.For example, if an unexpected phenomenon associated with blood pressuremedicine is hair growth, then the use of blood pressure medicine may beexpanded to include use as a hair is tonic. By comparison, expanded usesfor a medical product or device are not created by discovery of adverseevents, rather such uses are determined by performing extensive clinicaltrials and obtaining regulatory approval for marketing the new use ofthe product or device. On the other hand, the invention is intended toencompass a restricted use, i.e., avoiding, when possible, use of theproduct or device by methods involving same, or by use using same, hatare at increased risk for an adverse event. A new useful characteristicof a product or device responsive to identifying an essential adverseevent, e.g., providing a written waning with the product to a consumer,is also encompassed by the invention. New restricted uses are primarilyderived by discovering an adverse event because manufacturers arerequired to disclose possible adverse events associated with use of aproduct or device, even if the adverse event has not been proven tooccur in a specific risk group or situation. However, the invention isintended to encompass a use that allows a group, previously consideredto be at high risk, to use a product by better defining the high riskgroup, although, this is neither an expanded nor a restricted use.

It is also not the intent of this invention to encompass the simplecopyrighting package inserts that may contain adverse event information.A manufacturer and/or distributor is entitled to the copyrightassociated with any creative work that it produces, including packageinserts. Of course, package inserts may contain adverse eventinformation or product uses that are not proprietary and are in thepublic domain. This invention is, therefore, not intended to encompassthis practice. It is also not the intended purpose of the presentinvention to encompass proprietary kits (i.e., patented), wherein thekit is proprietary solely because of pre-existing intellectual propertyrights. Rather, it is the intent of the invention to claim proprietarykits containing new proprietary adverse event information and/orinstructions to use the product according to a proprietary new use basedon new adverse event information, wherein that new adverse eventinformation is the product of a system, device or method of the presentinvention.

Users might seek patent protection for new therapeutic uses for existingproducts or devices based on newly discovered essential adverse eventinformation. Similarly, users might seek protection for new labelingnecessitated by the discovery of the new essential adverse eventinformation. For any new use discovered by the systems according to thepresent invention, the instructions accompanying the product or devicefor which the new use is identified should desirably warnnewly-identified high risk users of the product or device to avoid usingthe product or device. Likewise, the instructions also inform users whowere previously but wrongly identified as high risk users that theproduct or device may be safely used by them. Preferably, systems 10,110 and 210 are capable of formatting the proprietary information datasuch that it is suitable for incorporation into the aforementionedintellectual property documents.

In FIG. 6, method steps 26′, 28′ and 30′ are identical to theircounterparts in FIG. 5. However, as indicated at step 32″ of FIG. 6, theowner or user of the proprietary essential adverse informationcommercializes the proprietary information by manufacturing (or causingto be manufactured) products or devices incorporating the proprietaryinformation and then selling the products and devices.

In addition to the functions represented by method steps 26′, 28′, 30′,32′ and 32″, additional tasks are preferably performed to morecompletely fulfill the purposes of the present invention, as reflectedin FIGS. 5 and 6. For example, as indicated by step 29′ in FIG. 5,server 14, 114 or 214 may be programmed to generate proprietaryinformation, typically in textual and/or graphic form, that isincorporated into intellectual property, sale and/or licensingdocuments. The documents then are used in negotiations with product ordevice manufacturers and/or distributors or other interested thirdparties. Additionally, FIG. 5 reveals in step 31′ that server 14, 114 or214 may optionally generate printed product warning information derivedfrom the essential adverse information database(s). The printed warninginformation may be used in connection with packaging such as, forexample, as product labeling or as product packaging inserts to advisethe consumer (or product prescriber in the case of products or devicesrequiring a prescription) of contraindications or other adverse eventsassociated with use of the product or device. Alternatively, as shown instep 33′ of FIG. 5, the owner of the proprietary information or itslicense may generate the aforesaid printed warning information.

Similarly, in FIG. 6, the server 14, 114 or 214 may generate proprietaryinformation that may be incorporated into intellectual property and/orsale documents (step 31″). Printed product warning or safety informationis generated by the servers 14, 114 or 214. Alternatively, as shown atstep 33″, this step is performed by the owner or license of theproprietary information (who also manufactures and/or distributes theproduct or device or causes it to be manufactured and/or distributed).

Equipped with the new essential adverse information generated by systems10, 110 and 210, a user might also urge the FDA to compel existingmanufacturers and/or distributors of a product to remove the productfrom the market if it does not have adequate safety warnings or toprevent those contemplating marketing the product from entering themarket without providing adequate safety labeling.

In a preferred application, the systems described herein are used todevelop new proprietary safer uses for drugs that are already generic orsoon to become generic. A generic drug is one where the active compoundeither is not protected by a composition of matter patent, or the patentwill very soon expire. Therefore the active compound is commerciallyavailable and adverse event data may be available from one or moresources. In some instances there are drugs that are on the market butprotected by orphan drug status, such as thalidomide or by at use patentsuch as AZT. In these instances the composition of matter patent hadexpired but competitors have not entered the market because there areonly a few known existing uses for the product, and these are covered byuse patents or orphan drug provisions. However, these drugs may havebeen on the market for ten or more years and little research has beenconducted before or during that time to identify and optimize thefullest extent of their potential ranges of safe use. Moreover, theyhave probably been tested for other indications, and adverse eventinformation exists on them.

In varying degrees, generics of a proprietary drug often differ from theproprietary drug itself, and from one another. More particularly,although their active ingredients may be the same, generic drugs mayinclude impurities, inert substances, carriers and other agents that arenot present in their corresponding proprietary drugs or other genericalternatives thereof. When considering generics and their proprietarycounterparts based solely on their active ingredients, the genericswould be expected to exhibit similar adverse events. However, throughimplementation of the present invention, generic drugs can be preciselycompared against their to proprietary drug counterparts, and alternativegenerics, to determine the impact of their inactive ingredients onadverse events, despite the variability of such inactive ingredients.For instance, drugs with agents which delay the release of an activeagent can be expected to exhibit many of the same side effects as drugswith the same active ingredient, but that release it over a shorterperiod of time. In this context, therefore, a generic and a proprietarydrag is considered to be the same product if the adverse event(s) and/ornew use(s) for the drugs would be expected to be consistent for both.

The “new use” derived from the new adverse event may involve restrictingthe use of the product or device in was that are now discovered to bedangerous. For example, if a product is determined to be flammable orexplosive, the “new proprietary use” would restrict its use inconditions that could lead to combustion or explosion, which may occurwhen used in the presence of an open flame or near a fire. Substancesdiscovered to emit toxic fumes would, as a new use, only be utilized inwell-ventilated areas, or under safety hoods. The new use may includeproviding a kit which contains warnings about a new adverse eventrelating to use of the product or device.

The term ‘commercially available’ pertains to products or devices thatare available to more than one group or company. The product can be asubstance, such as a drug, which is known by more than one company orresearch group. With such a product or device, adverse event data mayhave been generated by more than one group, and adverse, event dataalthough generated by one group, may not be new. This is because anotherearlier group may have discovered the adverse event first. This isespecially true when the product has been said commercially, and isknown to have been used by a number of different groups over time.

Studies may be performed with non-commercially available products,wherein a non limiting example would be drugs. In this example, thenon-commercially available drug may also be tested in patients receivingcommercially available drugs. Drug interactions may be detected betweenthe commercially available drug and the non-commercially available drug.In this situation the purpose of the study is to screen a database foradverse events of the non-commercially available product, not thecommercially available product. A manufacturer and/or distributor of acommercially available product or device is not required to warnpotential users about an interaction that may occur with their productor device and a product or device that is not yet available, or that themanufacturer or distributor does not even know exists. The presentinvention is intended for screening of products that are bothcommercially available and those that are not, unless otherwisespecified.

Many entities, large and small, may beneficially utilize the systemsdescribed herein. A representative, although non-limiting, example wouldbe an independent non-manufacturing company that procures access to oneor more essential adverse event databases to analyze the data containedtherein and identify new uses for existing drugs. The independentcompany could then license the “new use” technology or newcharacteristic it discovers to pharmaceutical manufacturers. The contentof the licensing agreements may be agreed upon before or after the datahas been analyzed. The independent company may opt to file appropriateintellectual property documents such as patent applications covering thenewly-discovered uses for the product and/or their attendant productwarning information and receive monies derived from the sale of the drugin the form of royalties or a lump sum fee.

Alternatively, the independent company may utilize the services of acontract manufacturer that will make the drug for the independentcompany which will reserve the right to sell the product on its ownbehalf. The independent company may also be a large insurer orpharmaceutical company that has access to its own extensive adverseevent information database(s) from which may identify and commerciallyexploit new uses for existing products or devices.

As mentioned above, the present systems and methods are also utilized todevelop proprietary safety information on products or devices unrelatedto the medical fields since manufacturers and/or distributors in otherfields of endeavor generally are required to provide consumers withsafety information regarding their products.

Essential Adverse Event Information

The final determination of what is “essential” information is determinedby a regulatory agency such as the FDA.

New adverse event information that is “essential” is of great commercialvalue since if this information is proprietary, for example patented inthe form a new use, it can be used to exclude potential competitors fromselling a product which would require the essential information. Inorder for a company searching through raw adverse new uses, to maximizeprofits from such a search, the “essential” new uses should ideally beseparated from other new uses. By limiting the protection for such newdata e.g., patenting, and limiting petitions to regulatory agencies toonly the “essential” new uses, a company saves time and money byavoiding expending time on adverse event information that has littlecommercial value.

Methods of Determining Essential Adverse Events

A computer system can assist identifying essential adverse eventinformation. Preferably the first step is to identify adverse eventsassociated with a group or subgroup using or exposed to the product inquestion.

In accordance with the embodied invention, comparisons are maderegarding the risk of the occurrence of a new adverse event in a groupof subjects exposed to the product or device, with the occurrence of thesame event in a control group. One type of control could be a groupexposed to a competing technology (drug, product). For example, if thesystem is evaluating the use of a fuel, then the control group would beexposed to a competing fuel, such as oil vs. coal vs. natural gas versuselectricity. In a like manner, the system could compare those exposed toan oil-based paint versus a latex-based paint as a non-limiting example.

Another type of control group could be a group that receives no exposureto a competing technology. For example, comparing a group receiving adrug, to a group receiving no drug.

A third possible control situation would be a population exposed to theproduct, in question, but selecting a subpopulation, which does notcontain people in the same subgroup in which the adverse event, isthought to occur more frequently. An example would compare a populationreceiving 4 doses of a vaccine, to a population receiving only one doseof a vaccine, which is either equal to a bolus of all 4 of thecomparable doses, or which is equal to only one of the comparable fourdoses. Another example would compare a group of people with liverproblems, receiving a drug for a non liver ailment, to a group withhealthy livers who receive the same drug.

A fourth type of control would use the group members as their owncontrol. In this case the incidence of an essential adverse eventoccurring prior to exposure to the product or device, is compared toessential adverse events following exposure to the subject product ordevice.

Having estimated the risk of an adverse event associated with a product,such as a drug, one can determine if the adverse events are essentialseveral different criteria can be utilized to determine if the adversereaction is essential. Such criteria include the non limiting examples,comprising: determining whether the adverse event is unnecessary, if therisk exceeds benefit, if causation has been proven, or if the risk isfrequent and or severe. These factors can be determined, and compared orcompiled with the assistance of a computer.

An ‘unnecessary adverse event’ would be an essential adverse event thatcould be or could have been easily avoided. One example would be a druginteraction, which could be avoided by withholding one of theinteracting drugs. Another example of an unnecessary adverse event isone in which the adverse event can be or could have been avoided byusing a different product, or even a different brand. For example, if adrug is very toxic in a subgroup of people, e.g., people of a certainage, or those who have a preexisting condition, then the adverse eventin such individuals groups can be or could have been easily avoided byusing a different drug or different treatment, for example, surgery.

Another type of essential adverse event information is one in which therisk ‘exceeds the benefit.’ For example, in certain subgroups ofpatients, the risk of disease or complications exceeds the benefitprovided by the product or device.

A third type of essential adverse event information is where thefrequency of the adverse event is so high, or the event so severe, thata significant health concern or medical management issue, in a situationthe adverse event may occur gradually, but laboratory testing could pickup the damage early, so that thither damage need not occur. Thefrequency of the events that render an adverse event essential dependsin part on the severity. Association between death, hospitalization,life threatening events, permanent organ damage, disability, cancer, orbirth defect and a product or device, becomes essential adverse eventinformation at a lower frequency than would the information relating toa potentially benign adverse event, such as but not limited to minorpain, swelling, and fever. Other adverse events that are included inthis essential category include marked abnormalities in laboratoryvalues, vital signs, EKG, and seizures.

A fourth type of essential adverse event information occurs when theadverse event is so well characterized that causation is generallybelieved to exist. For example, such a situation can occur when theadverse event is detected in two separate, well-controlled clinicaltrials, i.e., the adverse events are duplicated. An example would be anindustrial chemical, wherein exposure is unintended, but for whichexposure is known to cause severe adverse events. By providing warnings,one can alert those who may be exposed of the risks associated withaccidental exposure, and the treatment that should be under taken tominimize an adverse event following exposure.

Method of Screening for a Specific Adverse Event, Especially anEssential Adverse Event

The method of the preferred embodiment can be utilized to develop newmethods of screening drugs for adverse events, particularly essentialadverse events. The discovery of an essential adverse event warrantsthat all manufacturers and/or distributors of the product or genericversion to warn of the adverse event. In certain circumstances where acompetitor produces a similar or even identical (generic) the competitormay be given the choice of warning potential consumers of the adverseevent, or of performing a study to disprove the product is related to orcauses the adverse event, or disprove the that adverse event isessentials in the later case this embodiment pertains to specific teststo insure a product is safe, which comprises specifically checking tosee if the product is associated with or causes the adverse event whichis also associated with the competing product.

A competitor can perform specific tests to try to disprove the existenceof an essential adverse event. This can be of value to a competitor whenan adverse event information is covered in a patent (i.e., proprietaryadverse event), and inclusion of this adverse event in a product datasafety sheet (for example pharmaceutical labeling/package insert or anadvertisement) or an instruction brochure, pamphlet or book for adevice, would constitute an ant of infringement. Alternatively, acompetitor can perform a study to either try to disprove the existenceof an adverse event or try to disprove that the adverse event is‘essential,’ in the later ease the competitor may use the same ordifferent data as was used in establishing the adverse event in thefirst place, or that established that the adverse event is essential.The competitor can also use the same or different epidemiologicalmethod, and the same or different statistcal tests. Moreover, thecompetitor can provide additional data to supplement the initial data,such as information regarding confounding variables that may be usefulfor disproving the essential adverse event information. Computers canassist in this process as provided above.

By avoiding the placement of proprietary adverse event informationproduct data safety sheet or the like, a competitor avoids infringementof patents. This is because what was claimed as an essential element inthe patent or what appeared to be inherent in the claimed invention, isno longer required in the competitors product. Such an improvement willavoid costly patent litigation and lead to lower costs of development ofa product or device, quicker time from development to market, or anexpected higher return for development costs.

Nevertheless, the present invention is not intended to encompasspharmacogenomic techniques for screening.

Licensing Agreements

The invention provides new methods of business that provide to amanufacturer and/or distributor the ability to prevent a third-party,potential competitor from generating proprietary ‘essential’ informationwith regard to the manufactured or distributed product or device,thereby preventing the manufacturer's and/or distributor's exclusionfrom the market. A preferred embodiment of this method involves using alicensing agreement/contract for sales of the product or device, whichstates that the product or device an only be used for certain purposes.Such a license would exclude the licensee's right to the use the productor device to determine new proprietary characteristics or uses for thesubject product or device, for the situation in which the newcharacteristic or use is discovered by screening for the occurrences ofnew adverse events related to the use of the product or device.

The license or agreement could be similar to that used with software(e.g., a shrink wrap license), where the breaking of the wrapper or of aseal indicates one's acceptance of the contract. Such a licensingagreement could be affixed to or accompany the product or device, bymethods well known in the art. Alternatively, it could be signed by aresponsible party prior to delivery of the product or device to apurchaser, end-user, distributor, etc. Moreover, as part of thecontract/licensing agreement, the purchaser, end-user, distributor, orthe like, would agree for a predetermined period of time not to use theproduct or device in any attempt to discredit the existence done or morene essential adverse events, or the utility or the existing subjectproprietary use.

This will prevent competitor licensees from trying to block the originalowner's rights to the product or device by ‘discovering’ through the useof essential adverse event information, proprietary new characteristicsor uses of the product or device. For example, if the competitor were tofind or become aware of a previously unknown, essential adverse event,and if that information were proprietary to the competitor, such acompetitor could have a basis for claiming exclusive rights to a novelproduct or device, which would be just like the original, except itclaims anew characteristic based upon the newly discovered essentialadverse event information. However, the agreement controlling rights touse the product or device would preclude such behavior.

Alternatively, or in addition to an end-user agreement, a licensingagreement can be made at the time of intermediate sales of products ordevices to wholesalers, retailers, distributors or other who purchasethe product or device with the intent of reselling it to third parties.Such an agreement can be in the form of, or include, an electronicmonitoring system. In one such embodied electronic system, a windowwould appear or a button would require activation, acknowledgingacceptance of, and intent to comply with, the contract/licensingagreement. In an alternative embodiment, an electronic signature,acknowledging acceptance of and compliance with the agreement would bestored. In a third possible electronic method, an electronic image of an‘executed’ agreement document would be saved.

A manual packaging system can also be established which could beutilized in shipments to purchasers of large quantities of the productor device, such as but not limited to wholesalers, retailers, middleman,merchandisers, distributors and the like. A seal could he applied to thehulk package, that when broken, would certify agreement with a licensingagreement of the type(s) described above.

Based upon this disclosure, one skilled in the art can devise any of anumber of different methods or systems to accomplish the task ofcreating and/or verifying an agreement, electronically or otherwise,that would prevent the purchaser and/or the end-user from using theproduct or device in certain ways or for certain purposes, specificallyfor generating proprietary new, essential adverse event information tobe used for the identification and/or development of new characteristicsor uses of the subject product or device, and/or new methods ofscreening such products or devices for such new, essential adverse eventinformation.

Methods of Screening Adverse Events For Commercial Value.

All essential adverse event information is not of equal value. Valuedepends on the potential value of making a generic product or deviceinto a proprietary product or device, or preventing a proprietaryproduct or device from becoming a generic product or device. If aproprietary product or device is loosing money or marginally profitable,then extending its proprietary status by discovering essential adverseevents will add little value. For example, discovering an essentialadverse event in a generic aluminum-containing antacid may not bringmuch added profit, even if the product were to become proprietary, ifconsumers were more interested in switching to other antacids lackingaluminum, such as calcium-based antacids or magnesium-based antacids.Alternatively, a consumer with gastritis who is faced with theproposition of buying expensive antacids, may prefer to use alternativenewer, more expensive, and more effective products, such as histamineblockers or hydrogen pump inhibitors. Alternatively, large profits canbe made on a highly profitable patented product or device by extendingits proprietary status by obtaining one or more new patents based uponthe discovery of essential adverse events associated with use of theproduct or device.

In a preferred embodiment of the invention, a product or device forwhich an essential adverse event is discovered, is also one that ishighly profitable, but would face a marked decrease in profitability ifthe product or device were to lose its proprietary status. One skilledin the art can screen products or devices by recognized methods todetermine the potential value of discovering proprietary essentialadverse events. Those skilled in e.g., sales, marketing, licensing,statistics or business practices, will know how to use recognizedmethods to calculate or estimate such parameters as, in the non limitingexamples of current market share, potential market share, total marketshare in unit volume or sales, marketing costs, elasticity of demand,cost of production, cost of marketing, number of competitors, marketpotential, cost of discovering a new adverse event, product liabilitycosts, growth of market and the like. Mathematical modeling, with orwithout the use of computers, can be performed to evaluate whether itwould be profitable to develop a proprietary essential new use based onan essential new adverse event. In addition to profitability, an entitymay desire to determine cost of capital and opportunity costs beforedeciding to move forward with the project.

All references cited herein, including journal articles or abstracts,U.S. or foreign patents, published patent applications, or any otherreferences, are entirely incorporated by reference herein, including alldata, tables, figures, and text presented in the cited references.Additionally, the entire contents of the references cited within thereferences cited herein are also entirely incorporated by reference.

It is to be understood that the phraseology or terminology herein is forthe purpose of description and not of limitation, such that theterminology or phraseology of the present specification is to beinterpreted by the skilled artisan in light of the teachings andguidance presented herein, in combination with the knowledge of one ofordinary skill in the art. Reference to known method steps, conventionalmethods steps, known methods or conventional methods is not in any wayan admission that any aspect, description or embodiment of the presentinvention is disclosed, taught or suggested in the relevant art.

While the foregoing specification has been described with regard tocertain preferred embodiments, and many details have been set forth forthe purpose of illustration, it will be apparent to those skilled in theart that the invention may be subject to various modifications andadditional embodiments, and that certain of the details described hereincan be varied considerably without departing from the spirit and scopeof the invention. Such modifications, equivalent variations andadditional embodiments are also intended to fall within the scope of theappended claims.

What is claimed is:
 1. A new use for a product or device, wherein atleast one pre-existing or planned use for the product or device risksoccurrence of at least one adverse events associated with such use,wherein the risk is as determined from at least one essential adverseevent information database, wherein the data therein is derived from ananalysis of data from at least one adverse event computerized datasource, and identifies at least one new essential adverse eventassociated with the product or device, based upon essential adverseevent information stored in the data source, said new use comprisingcommercializing at least one use that differs from the pre-existing orplanned use by disclosing or avoidance of the at least one identifiedessential adverse event associated with the product or device wherecommercialization means creating profit from the exclusive disclosure ofsaid use and or adverse event where an essential adverse event is onethat must be disclosed in the information accompanying the product. 2.The new use according to claim 1, wherein the commercializing comprisesformatting the data relating to the at least one new adverse event thatis avoided by the new use of the product or device, or documenting same,such that a manufacturer or distributor of the product must informconsumers, users or individuals responsible for the user, physicians orprescribers about the at least one new adverse event that is avoided. 3.The new use according claim 1, wherein at least one data sourcecomprises raw commercial data.
 4. The new use according to claim 1,wherein at least one data source comprises information relating topatents and or patent applications.
 5. The new use according to claim 1,wherein at least one new use o the product or device is a restricteduse, restricting (or decreasing use) in at least one populationsubgroup, wherein there is observed to be a high risk of at least oneadverse event associated with exposure to or pre-existing use of theproduct.
 6. The new use according to claim 1, without a need for anexperimental or clinical study to verify or to test the new use.
 7. Thenew use according to claim 1, wherein the new use is protected bypatents and or patent applications.
 8. A proprietary new use accordingto claim 7 wherein the new use occurs in one or more subgroups ofconsumers, and wherein the new use is based on demographic data, butadditional testing of the consumers is not needed beforecommercialization of the new use.
 9. The new use according to claim 4,wherein the at least one new adverse event comprises a drug interaction,and wherein the new use is protected as an intellectual property. 10.The new use according to claim 4, wherein the at least one new adverseevent is other than a chronic immune mediated disorder, and wherein thenew use is protected as an intellectual property.
 11. The new useaccording to claim 1, wherein the new use is protected as anintellectual property, and wherein commercializing the new use furthercomprises documenting inventorship.
 12. The new use according to claim1, wherein the new use is one other than a new dosing regimen, andwherein the new use is protected as an intellectual property.
 13. Thenew use according to claim 4, further comprising determining a value ofcommercializing the at least one new use that avoids the at least oneidentified essential adverse event.
 14. The new use according to claim13, wherein the product or device is commercially available, and furthercomprising identifying the new use as a restricted use in at least onepopulation subgroup when there is observed to be a high risk of at leastone adverse event associated with the pre-existing use of the product ordevice.
 15. The new use according to claim 9, wherein the product ordevice is commercially available, and further determining a value ofcommercializing the at least one new use.
 16. The new use according toclaim 1, wherein the commercializing comprises selling, leasing orlicensing the newly identified product information.